JP2014221064A5 - - Google Patents
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- JP2014221064A5 JP2014221064A5 JP2014137893A JP2014137893A JP2014221064A5 JP 2014221064 A5 JP2014221064 A5 JP 2014221064A5 JP 2014137893 A JP2014137893 A JP 2014137893A JP 2014137893 A JP2014137893 A JP 2014137893A JP 2014221064 A5 JP2014221064 A5 JP 2014221064A5
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- antibody
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- functional fragment
- mesothelin
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- 102000004965 antibodies Human genes 0.000 claims description 27
- 108090001123 antibodies Proteins 0.000 claims description 27
- 102000003735 mesothelin Human genes 0.000 claims description 9
- 108090000015 mesothelin Proteins 0.000 claims description 9
- 239000000427 antigen Substances 0.000 claims 4
- 102000038129 antigens Human genes 0.000 claims 4
- 108091007172 antigens Proteins 0.000 claims 4
- 210000004027 cells Anatomy 0.000 claims 4
- 108020004707 nucleic acids Proteins 0.000 claims 3
- 150000007523 nucleic acids Chemical class 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000035693 Fab Effects 0.000 claims 1
- 230000001580 bacterial Effects 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 210000004962 mammalian cells Anatomy 0.000 claims 1
- 239000000546 pharmaceutic aid Substances 0.000 claims 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- HOGDNTQCSIKEEV-UHFFFAOYSA-N N'-hydroxybutanediamide Chemical compound NC(=O)CCC(=O)NO HOGDNTQCSIKEEV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
Description
実施例２：エピトープのグループ化
エピトープのグループ化の実験を、固定化したメソセリンに対する抗メソセリン抗体の対の同時結合をモニタリングすることによって、Ｂｉａｃｏｒｅを使用して実施した。つまり、第１の抗体をｎ−ヒドロキシスクシンアミド（ＮＨＣ）およびＮ−エチル−Ｎ’−ジメチルアミノプロピルカルボジイミド（ＥＤＣ）を使用する１級アミンを介して、センサーチップに共有結合により固定化した。表面の占有されていない結合部位をエタノールアミドを用いてブロックした。可溶性メソセリンを固定化した抗体を介して表面にて捕獲し、捕獲した抗体のエピトープを、全ての結合したメソセリン分子についてブロックした。ただちに、第２の抗体を表面に通し、固定化したメソセリンに結合させた。同じまたは重複するエピトープを認識する２つの抗体は、メソセリンに結合できない一方、異なるエピトープを有する抗体は結合可能である。抗体表面を、グリシン、ｐＨ２．８を用いて再生し、結合したタンパク質を除去し、次いで、プロセスを他の抗体を用いて繰り返した。７つの抗体の全ての組合せを試験した。ＭＦ−Ｔおよび７つの他の抗体を使用した代表的な結果を図１Ａに示す。第２の抗体としてのＭＦ−Ｔの使用は、ポジティブコントロールとして機能し、抗ＦＬＡＧはネガティブコントロールとして機能した。図１Ｂは、各エピトープを示す円を有するＶｅｎｎダイアグラムにて、７つの抗メソセリン抗体についての対での結合結果の概要を示す。重複した円は、重複したエピトープを示す。ＭＦ４２８は、結合について、試験した他の全ての抗体と競合した。ＭＦ−ＪおよびＭＦ−Ｔは、互いに、およびＭＦ−Ａ、ＭＦ−２２６およびＭＦ−Ｌとは異なるエピトープに結合し、これらＭＦ−Ａ、ＭＦ−２２６およびＭＦ−Ｌは、同じエピトープ領域について競合しているようである。市販のマウス抗体Ｋ１は、ＭＦ−ＪおよびＭＦ−Ｔによって認識される領域と異なるエピトープ領域に結合しているが、ＭＦ−Ａ、ＭＦ−ＬおよびＭＦ−２２６と類似のエピトープ領域を有しているようである。
Example 2: Epitope Grouping Epitope grouping experiments were performed using Biacore by monitoring the simultaneous binding of anti-mesothelin antibody pairs to immobilized mesothelin. That is, the first antibody was covalently immobilized on the sensor chip via a primary amine using n-hydroxysuccinamide (NHC) and N-ethyl-N′-dimethylaminopropylcarbodiimide (EDC). . Unoccupied binding sites on the surface were blocked with ethanolamide. Soluble mesothelin was captured on the surface via an immobilized antibody and the epitope of the captured antibody was blocked for all bound mesothelin molecules. Immediately, the second antibody was passed through the surface and bound to immobilized mesothelin. Two antibodies that recognize the same or overlapping epitopes cannot bind mesothelin, while antibodies with different epitopes can bind. The antibody surface was regenerated with glycine, pH 2.8 to remove bound protein, and the process was then repeated with other antibodies. All combinations of 7 antibodies were tested. A representative result using MF-T and 7 other antibodies is shown in FIG. 1A. Use of MF-T as a second antibody served as a positive control and anti-FLAG served as a negative control. FIG. 1B shows a summary of paired binding results for seven anti-mesothelin antibodies in a Venn diagram with circles representing each epitope. Overlapping circles indicate overlapping epitopes. MF428 competed with all other antibodies tested for binding. MF-J and MF-T bind to each other and to a different epitope than MF-A, MF-226 and MF-L , which compete for the same epitope region It seems to be doing. The commercially available mouse antibody K1 binds to an epitope region different from the region recognized by MF-J and MF-T, but has an epitope region similar to MF-A, MF-L and MF-226. Seems to be.
Claims (12)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US437807P | 2007-11-26 | 2007-11-26 | |
| US61/004,378 | 2007-11-26 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010535269A Division JP5608091B2 (en) | 2007-11-26 | 2008-11-19 | Anti-mesothelin antibodies and uses thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018038254A Division JP6717869B2 (en) | 2007-11-26 | 2018-03-05 | Anti-mesothelin antibody and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2014221064A JP2014221064A (en) | 2014-11-27 |
| JP2014221064A5 true JP2014221064A5 (en) | 2016-03-31 |
Family
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Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010535269A Active JP5608091B2 (en) | 2007-11-26 | 2008-11-19 | Anti-mesothelin antibodies and uses thereof |
| JP2014137893A Pending JP2014221064A (en) | 2007-11-26 | 2014-07-03 | Anti-mesothelin antibodies and use thereof |
| JP2018038254A Active JP6717869B2 (en) | 2007-11-26 | 2018-03-05 | Anti-mesothelin antibody and uses thereof |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010535269A Active JP5608091B2 (en) | 2007-11-26 | 2008-11-19 | Anti-mesothelin antibodies and uses thereof |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018038254A Active JP6717869B2 (en) | 2007-11-26 | 2018-03-05 | Anti-mesothelin antibody and uses thereof |
Country Status (31)
| Country | Link |
|---|---|
| US (3) | US9023351B2 (en) |
| EP (3) | EP2215121B1 (en) |
| JP (3) | JP5608091B2 (en) |
| KR (1) | KR101559599B1 (en) |
| CN (2) | CN104151429B (en) |
| AU (1) | AU2008329221B2 (en) |
| BR (1) | BRPI0819909B8 (en) |
| CA (1) | CA2706529C (en) |
| CO (1) | CO6280409A2 (en) |
| CR (1) | CR11456A (en) |
| CU (1) | CU23833A3 (en) |
| CY (1) | CY1117437T1 (en) |
| DK (1) | DK2215121T3 (en) |
| DO (1) | DOP2010000150A (en) |
| EC (1) | ECSP10010191A (en) |
| ES (1) | ES2569513T3 (en) |
| GT (1) | GT201000148A (en) |
| HK (2) | HK1148541A1 (en) |
| HN (1) | HN2010001062A (en) |
| HR (1) | HRP20160485T1 (en) |
| HU (1) | HUE027358T2 (en) |
| IL (1) | IL205681A0 (en) |
| MA (1) | MA31862B1 (en) |
| MX (1) | MX2010005603A (en) |
| MY (1) | MY157164A (en) |
| NZ (1) | NZ585551A (en) |
| PL (1) | PL2215121T3 (en) |
| SI (1) | SI2215121T1 (en) |
| TN (1) | TN2010000234A1 (en) |
| UA (1) | UA106036C2 (en) |
| WO (1) | WO2009068204A1 (en) |
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| WO2006124641A2 (en) * | 2005-05-12 | 2006-11-23 | The Government Of The United States, As Represented By The Secretary Of Health And Human Services, National Institutes Of Health | Anti-mesothelin antibodies useful for immunological assays |
| DK1888643T3 (en) | 2005-05-18 | 2015-01-05 | Morphosys Ag | Anti-GM-CSF antibodies as well as their uses |
| BRPI0611220A2 (en) * | 2005-06-02 | 2010-08-24 | Astrazeneca Ab | antibodies directed to cd20 and uses thereof |
| KR101554848B1 (en) * | 2007-10-01 | 2015-09-21 | 브리스톨-마이어스 스큅 컴퍼니 | Human antibodies that bind mesothelin, and uses thereof |
| DK2215121T3 (en) * | 2007-11-26 | 2016-05-02 | Bayer Ip Gmbh | ANTI-mesothelin ANTIBODIES AND USES THEREOF |
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